Tissue- and stage-specific landscape of the mouse translatome

Abstract

The current understanding of how overall principles of translational control govern the embryo-to-adult transition in mammals is still far from comprehensive. Herein we profiled the translatomes and transcriptomes of six tissues from the mice at embryonic and adult stages and presented the first report of tissue- and stage-specific translational landscape in mice. We quantified the extent of gene expression divergence among different expression layers, tissues and stages, detected significant changes in gene composition and function underlying these divergences and revealed the changing architecture of translational regulation. We further showed that dynamic translational regulation can be largely achieved via modulation of translational efficiency. Translational efficiency could be altered by alternative splicing (AS), upstream and downstream open reading frames (uORFs and dORFs). We revealed AS-mediated translational repression that was exerted in an event type-dependent manner. uORFs and dORFs exhibited mutually exclusive usage and the opposing effects of translational regulation. Furthermore, we discovered many novel microproteins encoded by long noncoding RNAs and demonstrated their regulatory potential and functional relevance. Our data and analyses will facilitate a better understanding of the complexity of translation and translational regulation across tissue and stage spectra and provide an important resource to the translatome research community.

An Integrated Approach for Discovering Noncanonical MHC-I Peptides Encoded by Small Open Reading Frames

“…Four publicly available Ribo-seq data sets downloaded from the NCBI SRA database were used . Preprocessing of Ribo-seq raw data as previsourly reported, consisted of adaptor removal using Cutadapt (v1.8.1), low-quality trimming using Sickle (v1.33), and removal of rRNA and tRNA contaminants using Bowtie2 (v2.3.5.1) . All remaining reads were mapped to the human reference genome (GENCODE, Release 28: GRCh38.p12) using STAR (v2.5.2) with default parameters, and further uniquely mapped reads were extracted.…”

Casting CRISPR-Cas13d to fish for microprotein functions in animal development

“…Early stages of vertebrate development and vertebrate pluripotent stem cells show widespread short ORF translation. 17 , 32 , 33 , 38 , 54 , 79 , 80 Among many vertebrate model systems, zebrafish ( D. rerio ) has emerged as a premier model system because of its high offspring number, ex-utero development, and genetic tractability. Not to mention, zebrafish exhibit many conserved cellular, molecular, and genetic foundations of development, 81 and more than 70% of human genes have at least one ortholog in zebrafish, making zebrafish studies highly informative for human biology.…”

Widespread translational control regulates retinal development in mouse

“…Similar to transcription, translation involves a series of highly temporally orchestrated events directed by cis-elements and trans-factors ( 7 ). Increasing evidence emphasizes the importance of translation of gene expression ( 8 , 9 ). Dynamic, tight, and coordinated translational regulation can conduce to the growth of multicellular organisms, particularly during a rapid morphological transition, such as development of red blood cell ( 10 ), embryonic stem cell differentiation ( 11 ), cortical neurogenesis ( 12 ), myogenic differentiation ( 13 ) and spermioteleosis ( 14 ).…”